THE LIPOXYGENASE INHIBITOR ML351 AFFECTS CELL VIABILITY BY REGULATING AUTOPHAGY AND SEMAPHORIN SIGNALING PATHWAYS IN A549 CELLS

Yıl 2026, Cilt: 15 Sayı: 1 , 74 - 82 , 27.01.2026

Neslihan Meriç , Ezgi Kar , Ceyhan Hacıoğlu , Fatih Kar

https://doi.org/10.18036/estubtdc.1798104

https://izlik.org/JA25RF68HJ

Öz

Lung cancer is one of the leading causes of cancer-related deaths worldwide, and the inadequacy of current treatment strategies necessitates the investigation of new molecular targets. In this study, the effects of the selective 15-lipoxygenase inhibitor ML351 on cell viability, autophagy, and the Semaphorin-3E (SEMA3E) signaling pathway in A549 lung adenocarcinoma cells were examined.

Cell viability was evaluated using the MTT assay, and protein levels of autophagy markers (Beclin-1, LC3, and p62) and SEMA3E were measured using the ELISA method. The findings revealed that ML351 exhibited a dose-dependent cytotoxic effect. The IC₅₀ value was calculated as 92 µM, cell viability fell below 80% in the 20–80 µM range, and was almost completely eliminated at 160 µM (***p<0.001). Significant decreases in the levels of autophagy markers Beclin-1, LC3, and p62 were observed in both dose groups (**p<0.01). Additionally, while SEMA3E levels were ~20 ng/mL in the control group, they decreased to 12–13 ng/mL at 45 µM ML351 and became undetectable at 92 µM (***p<0.001).

These results suggest that ML351 suppresses adaptive cellular responses by inhibiting autophagy processes in lung cancer cells and limits the survival capacity of tumor cells by reducing Semaphorin signaling mediated by SEMA3E. Therefore, ML351 may be considered a novel therapeutic candidate in lung cancer biology; however, further studies using in vivo models and different cell lines are important to validate these findings.

Anahtar Kelimeler

ML351 , Autophagy , SEMA3E , A549

Kaynakça

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